Diagnostic evaluation of classification criteria for rheumatoid arthritis and reactive arthritis in an early synovitis outpatient clinic

OBJECTIVE: To evaluate the diagnostic performance of classification criteria for rheumatoid arthritis (RA) and reactive arthritis (ReA) in an early synovitis outpatient clinic. METHODS: In a prospective two year survey consecutive patients with early synovitis of less than one year duration were documented using a standardised registry and were classified after an expert diagnosis. Of a total of 320 patients 39 (19%) were diagnosed as having RA, 24 (11%) patients had ReA, 117 (54%) patients did not have an unequivocal diagnosis, and were considered as undifferentiated arthritis. RESULTS: The retrospective application of the revised 1987 ACR criteria for the classification of RA in this data set revealed a sensitivity of 90% and a specificity of 90%. The positive predictive value was 0.67, the negative predictive value 0.98. Similarly, the criteria for ReA of the French Society of Rheumatology (FSR) showed a sensitivity of 80% and a specificity of 90% with a positive predictive value of 0.55 and a negative predictive value of 0.97. Both criteria sets had a satisfying likelihood ratio of 9 and 10, respectively. CONCLUSION: Both the 1987 ACR criteria for RA and the criteria of the FSR for ReA have a reasonable diagnostic validity in patients with early synovitis, including a large portion of undifferentiated arthritis.     

Campylobacter reactive arthritis: a systematic review

OBJECTIVE: To review the literature on the epidemiology of Campylobacter-associated reactive arthritis (ReA). METHODS: A Medline (PubMed) search identified studies from 1966 to 2006 that investigated the epidemiology of Campylobacter-associated ReA. Search terms included: "reactive arthritis," "spondyloarthropathy," "Reiter's syndrome," "gastroenteritis," "diarrhea," "epidemiology," "incidence," "prevalence," and "Campylobacter." RESULTS: The literature available to date suggests that the incidence of Campylobacter ReA may occur in 1 to 5% of those infected. The annual incidence of ReA after Campylobacter or Shigella may be 4.3 and 1.3, respectively, per 100,000. The duration of acute ReA varies considerably among reports, and the incidence and impact of chronic ReA from Campylobacter infection is virtually unknown. CONCLUSIONS: Campylobacter-associated ReA incidence and prevalence varies widely among reviews due to case ascertainment differences, exposure differences, lack of diagnostic criteria for ReA, and perhaps genetics and ages of exposed individuals. At the population level it may not be associated with HLA-B27, and inflammatory back involvement is uncommon. Follow-up for long-term sequelae is largely unknown. Five percent of Campylobacter ReA may be chronic or relapsing (with respect to musculoskeletal symptoms).     

Human immunodeficiency virus related reactive arthritis in Zambia

OBJECTIVE: To characterize the clinical, radiological, and diagnostic features of reactive arthritis (ReA) in indigenous Black Zambians with human immunodeficiency virus (HIV) infection. METHODS: Consecutive patients attending an arthritis clinic over a 5-year period were studied prospectively. Those who satisfied diagnostic criteria for ReA were analyzed. RESULTS: In total, 170 patients satisfied the ESSG criteria for ReA; 71 (45 men, 26 women) had one or more extraarticular manifestations; 30% had enteroreactive and 14% uroreactive disease. Only 59% of patients had the diagnostic features of ReA at presentation. The initial diagnosis was undifferentiated spondyloarthropathy (uSpa) in 20%, other ReA in 14%, and "arthritis alone" in 7%. Of 65 (42 men, 23 women) patients tested, 94% were HIV-positive (91% men, 100% women). In those with HIV, the arthritis was predominantly polyarticular, lower limb-predominant, and progressive; 58% of 33 with persistent disease had erosions of foot and/or hand joints (average disease duration, 24.4 mo); 6 of 10 showed early radiological spine or sacroiliac joint changes (average duration 47.7 mo). Anterior uveitis occurred in 33% of patients, while keratoderma blenorrhagicum and stomatitis occurred in 14.3% and 9.5%, respectively, of patients with enteroreactive ReA. Uroreactive ReA was more common in women. There were no significant differences in the clinical, diagnostic, or radiographic features between men and women or between those with or without a known preceding trigger. CONCLUSION: HIV associated ReA in Black Zambians frequently follows an accelerated course with a strong tendency to relapse, develop early erosions and joint deformity, and become chronic. The clinical, diagnostic, and radiographic features are indistinguishable from those described in the conventional (HLA-B27 related) disease, although our HIV-positive patients have a high overall frequency of uveitis, keratoderma, and onycholysis.     

A wider spectrum of spondyloarthropathies

As in other diseases of undetermined etiology, the diagnosis of ankylosing spondylitis (AS) and related spondyloarthropathies (SpA) is based on clinical and roentgenographic features. The current criteria for diagnosis of some of these diseases are too restricted, and do not recognize the existence of a much wider disease spectrum. For example, radiographically detected sacroiliitis is extremely frequent in AS, but may not be an obligate manifestation, especially in early or atypical forms of the disease. Arthritis involving the axial skeleton, including the sacroiliac joints, can be present in some patients without evidence of erosive disease roentgenographically. The disease spectrum of Reiter's syndrome has also been broadened considerably, and "incomplete" forms of Reiter's syndrome are observed much more commonly than the classical triad of arthritis, conjunctivitis, and urethritis. The term "B27-associated reactive arthritis" has been used in recent years to refer to SpA following enteric or urogenital infections, and the disease spectrum includes the clinical picture of typical Reiter's syndrome. The clinical spectrum of psoriatic SpA has been better clarified. Some of the less well defined B27-associated clinical syndromes include seronegative oligoarthritis, polyarthritis, or dactylitis ("sausagelike" toes) of the lower extremities, and heel pain caused by calcaneal (and tarsal) periostitis. These and other undifferentiated SpA have been ignored in previous epidemiological studies because of the inadequacy of the existing classification criteria. The European Spondylarthropathy Study Group (ESSG) has completed a study aimed at developing preliminary classification criteria for the whole group of SpA patients, with the specific intention of encompassing patients with undifferentiated SpA.     

Psoriasis predicts a poor short-term outcome in patients with spondylarthropathy.

OBJECTIVE: The outcome of patients with recent-onset spondylarthropathy (SpA) is unclear. Therefore, the objective of this study was to prospectively correlate clinical and laboratory features with functional and radiologic outcome in patients with psoriatic SpA (PsS), undifferentiated SpA (uSpA), and Reiter's syndrome/reactive arthritis (ReA). METHODS: Patients presenting to an early arthritis clinic with a spondylarthropathy pattern of peripheral arthritis were selected and prospectively followed. Clinical and laboratory features were recorded at baseline, 12 months, and 24 months. Radiographs of affected joints were taken at presentation and at followup. RESULTS: The cohort consisted of 157 patients: 82 PsS, 59 uSpA, and 16 ReA. Symptom duration at presentation was progressively shorter, and the erythrocyte sedimentation rate/C-reactive protein (ESR/CRP) incrementally higher in ReA, uSpA, and PsS, respectively. There was a higher swollen joint count (SJC) in PsS compared with uSpA. In PsS, strong positive correlations were observed between ESR/CRP and articular indices. Initially, functional impairment was greater in ReA compared with uSpA and PsS but resolved completely in ReA. Clinical remission rates at 2 years were ReA 61% and uSpA 63%, compared with PsS 14%. Remission at 2 years could be predicted in SpA by disease category and presentation SJC. Baseline erosions in PsS (28%) and uSpA (5%) increased to 45% and 25%, respectively, at 2 years. CONCLUSION: These observations suggest a spectrum within the spondylarthropathy subgroups where at presentation the acute phase markers in ReA and uSpA reflect a systemic process, whereas in PsS they reflect articular manifestations. Although the clinical presentations are indistinguishable, PsS has a more aggressive clinical course with a poorer functional and radiologic outcome.     

Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondylarthropathies: a Department of Veterans Affairs cooperative study.

OBJECTIVE: To determine if the peripheral articular manifestations of the seronegative spondylarthropathies (SNSA) respond differently than the axial manifestations to treatment with sulfasalazine (SSZ). METHODS: This is a reanalysis of a previously reported series of randomized, double-blind, placebo-controlled, multicenter trials comparing the effects of SSZ, 2,000 mg/day, and placebo on the axial and peripheral articular manifestations of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and reactive arthritis (ReA; Reiter's syndrome). Patients were classified as treatment responders on the basis of meeting predefined improvement criteria in 4 outcome measures: namely, patient and physician global assessments in all patients, morning stiffness and back pain in patients with axial manifestations, and joint pain/tenderness scores and joint swelling scores in patients with peripheral articular manifestations. RESULTS: Six hundred nineteen SNSA patients (264 AS, 221 PsA, and 134 ReA) were studied. One hundred eighty-seven of these patients had only axial manifestations of their disease, while 432 patients had peripheral articular manifestations. Of the patients with axial disease, 40.2% of the SSZ group and 43.3% of the placebo group met the predefined response criteria (P = 0.67). Of the peripheral articular group, 59.0% of the SSZ-treated patients and 42.7% of the placebo-treated patients showed a response (P = 0.0007). CONCLUSION: In a large group of affected individuals, the response of SNSA patients to SSZ appears to be related to the articular manifestations of their disease. These data demonstrate that the axial and peripheral articular manifestations of SNSA respond differently to treatment with SSZ. In SNSA patients with persistently active peripheral arthritis, SSZ is safe, well tolerated, and effective.     

Reactive arthritis

Reactive arthritis (ReA) was known as Reiter's disease or Fiessinger-Leroy disease for nearly 100 years. However, during the past 30 years the disease has been known as reactive arthritis, a member of the spondyloarthritis family. Despite knowing the initiating event (infection) and genetic constitution (many patients have HLA-B27) of ReA, a model of interplay between environment and genetics, its pathogenesis is still incompletely known. This review covers the epidemiology, clinical features, treatment, and prognosis of ReA.     

The incidence of sexually acquired reactive arthritis: a systematic literature review

Reactive arthritis (ReA) is an inflammatory spondyloarthritis occurring after infection at a distant site. Chlamydia trachomatis is proposed to be the most common cause of ReA, yet the incidence of sexually acquired ReA (SARA) has not been well established. We therefore carried out a systematic literature review to collate and critically evaluate the published evidence regarding the incidence of SARA. MEDLINE and EMBASE databases were searched using free-text and MeSH terms relating to infection and ReA. The title and abstract of articles returned were screened independently by two reviewers and potentially relevant articles assessed in full. Data was extracted from relevant articles and a risk of bias assessment carried out using a validated tool. Heterogeneity of study methodology and results precluded meta-analysis. The search yielded a total of 11,680 articles, and a further 17 were identified from review articles. After screening, 55 papers were assessed in full, from which 3 met the relevant inclusion criteria for the review. The studies reported an incidence of SARA of 3.0–8.1 % and were found to be of low to moderate quality. More studies are required to address the lack of data regarding the incidence of SARA. Specific and sensitive classification criteria must be developed in order for consistent classification and valid conclusions to be drawn. In clinical practice, it is recommended clinicians discuss the possibility of ReA developing at the time of STI diagnosis and to encourage patients to return if they experience any relevant symptoms.     

Reactive arthritis

Reactive arthritis (ReA) can be defined as the development of sterile inflammatory arthritis as a sequel to remote infection, often in the gastrointestinal or urogenital tract. Although no generally agreed-upon diagnostic criteria exist, the diagnosis is mainly clinical, and based on acute oligoarticular arthritis of larger joints developing within 2-4 weeks of the preceding infection. According to population-based studies, the annual incidence of ReA is 0.6-27/100,000. In addition to the typical clinical picture, the diagnosis of ReA relies on the diagnosis of the triggering infection. Human leucocyte antigen (HLA)-B27 should not be used as a diagnostic tool for a diagnosis of acute ReA. In the case of established ReA, prolonged treatment of Chlamydia-induced ReA may be of benefit, not only in the case of acute ReA but also in those with chronic ReA or spondylarthropathy with evidence of persisting chlamydia antigens in the body. In other forms of ReA, there is no confirmed evidence in favour of antibiotic therapy to shorten the duration of acute arthritis. The outcome and prognosis of ReA are best known for enteric ReA, whereas studies dealing with the long-term outcome of ReA attributable to Chlamydia trachomatis are lacking.     

Juvenile idiopathic arthritides evaluated prospectively in a single center according to the Durban criteria

OBJECTIVE: Chronic arthritis in children represents a nonhomogeneous group of diseases with unknown etiology. To classify these patients in well defined diagnostic categories, a task force of the International League Against Rheumatism proposed a new classification with precise criteria. We analyzed the new criteria in children with chronic arthritis. METHODS: A cohort of children was prospectively and sequentially examined in a pediatric rheumatology clinic from April to June 1997. RESULTS: One hundred ninety-four children fulfilled the criteria of juvenile idiopathic arthritis and 80% of them (155 children) were classified in one of the 6 diagnostic categories. Seventeen children (9%) did not fit any other category and 22 (11%) could be classified in more than one category. The proportion of children fitting only one category was much lower for psoriatic arthritis and enthesitis related arthritis than for the other categories. CONCLUSION: Based on the results, we propose some modifications to the classification criteria. This new classification is an important tool for the diagnosis of chronic arthritis in children, but the criteria need further adjustments to improve the percentage of patients classified in one defined category.     

Frequency of recent parvovirus infection in patients examined for acute reactive arthritis. A study with combinatorial parvovirus serodiagnostics

OBJECTIVE: To determine the causative role of human parvovirus B19 as a preceding infection in patients examined for acute reactive arthritis (ReA). METHODS: Sixty adult patients with acute arthritis were screened for evidence of triggering infections. In all patients, cultures of stool specimens and of Chlamydia trachomatis in urethra/cervix, and/or bacterial serology were studied. The timing of primary infection of human parvovirus B19 was determined by measurement in serum of VP2-IgM, VP2-IgG, epitope-type specifity of VP2-IgG, and avidity of VP1-IgG. RESULTS: Median time from onset of joint symptoms to the rheumatological consultation was five weeks (range 1-62). Of the 60 patients, 35 fulfilled the diagnostic criteria for ReA; in the remaining, the diagnosis was unspecified arthritis (UA). Thirty-six patients had antibodies for the B19 virus. Occurrence of these antibodies did not differ significantly between ReA and UA groups (P = 0.61). Of these 36 patients, 34 had a pre-existing immunity to the B19 virus. Of the two other patients, one had rash and self-limiting polyarthritis with serological evidence of B19 primary infection, and the other had arthritis of the lower extremities with serological evidence of a convalescence period after the B19 primary infection. The latter patient also had antibodies to Yersinia, with a clinical picture typical for ReA. CONCLUSION: In patients examined for acute ReA, the frequency of recent B19 virus infection was 3.3% (2 out of 60). The diagnostic utility of the presented methodology, by using a single serum sample, was evident.     

Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in synovial tissue of arthritis patients.

OBJECTIVE: To assess the presence of Chlamydia pneumoniae DNA in the joints of patients with reactive arthritis (ReA) and other arthritides. METHODS: DNA was prepared from synovial tissue (ST) and several synovial fluid (SF) samples from 188 patients with either ReA, undifferentiated oligoarthritis, or other forms of arthritis, and from 24 normal (non-arthritis) individuals. Preparations were screened using polymerase chain reaction (PCR) assays that independently targeted the C. pneumoniae 16S ribosomal RNA and major outer membrane protein genes. RESULTS: Twenty-seven of 212 ST samples (12.7%) were PCR positive for C. pneumoniae DNA; 10 SF samples from these 27 patients were similarly positive. Among the PCR-positive patients, 3 had ReA, 2 had Reiter's syndrome, 7 had undifferentiated oligoarthritis, 4 had undifferentiated monarthritis, 6 had rheumatoid arthritis, and 5 had other forms of arthritis. No samples from normal control individuals were PCR positive. CONCLUSION: DNA of C pneumoniae is present in synovial specimens from some arthritis patients. The prevalence of this organism in the joints was lower than that of C trachomatis, and synovial presence of the organism was not associated with any distinct clinical syndrome. Widely disseminated nucleic acids such as those of C. pneumoniae might have some role in the pathogenesis of several arthritides, since the organism was not found in the ST from normal control individuals.     

Immune responses to Borrelia burgdorferi in patients with reactive arthritis

In reactive arthritis (ReA), including Reiter's syndrome, a close relationship between chronic enteric and genitourinary infections and the clinical features of enthesitis has been described. In contrast, in Lyme arthritis, a distinct clinical entity, chronic infection with the tick-transmitted spirochete Borrelia burgdorferi has been associated with the disease. In a prospective study, 51 patients with ReA were tested for evidence of chlamydial and spirochetal infection. The presence of Chlamydia was determined by culture in 8 patients, and 7 additional patients had markedly elevated antibody titers. In 9 patients, antibodies specific to B burgdorferi were found. Purified peripheral blood T lymphocytes of all 9 patients proliferated specifically to stimulation with macrophages pre-pulsed with B burgdorferi antigens. Compared with other protein antigens, higher numbers of antigen-pulsed macrophages were necessary to activate B burgdorferi-specific T cells. Although antibody titers decreased in response to antibiotic treatment in 8 of 9 patients, second-line therapy with sulfasalazine or methotrexate was required to obtain clinical remission. These data suggest that chronic infection with B burgdorferi can cause ReA. In predisposed individuals, the arthritogenic immune response might be triggered by persisting infectious agents independent of their antigenic specificities.     

The influence of heredity for psoriasis on the ILAR classification of juvenile idiopathic arthritis

OBJECTIVE: To evaluate how heredity for psoriasis influences classification according to the International League of Associations for Rheumatology (ILAR). Heredity for psoriasis is currently both an exclusion and an inclusion criterion for different types of childhood arthritis according to ILAR classification criteria. METHODS: Twenty physicians in 5 Nordic countries prospectively collected data from the incident cases in their catchment areas over an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: Of the 321 patients included who could be classified according to ILAR criteria for childhood arthritis, 50 (15.6%) patients were excluded from 55 classification events and fulfilled criteria for "other arthritis 1" i.e., did not fulfill criteria for any of the other classification categories, primarily because of heredity for psoriasis. If psoriasis in second degree relatives was disregarded as an exclusion criterion, only 8.7% of the patients remained in the "other arthritis 1" subgroup. For 20.6% of the whole group, heredity for psoriasis in a first or second degree relative (or both) and its distribution among arthritis subgroups did not differ except for juvenile psoriatic arthritis. CONCLUSION: We suggest that second degree heredity for psoriasis be withdrawn as an exclusion criterion from the ILAR criteria.     

Acute arthritis in Zimbabwean patients: possible relationship to human immunodeficiency virus infection

The clinical features of an acute arthritis in 20 Zimbabwean patients, 17 of whom fulfilled criteria for the diagnosis of complete or incomplete Reiter's syndrome, are described. Fourteen of 19 patients tested were positive for human immunodeficiency virus (HIV) antibodies and most had features of the AIDS related complex. None of 14 patients tested possessed the HLA-B27 tissue antigen commonly associated with Reiter's syndrome. The relationship between HIV infection, immunogenetic factors and the arthropathy we have observed remains to be elucidated.     

Chlamydial associated syndrome of arthritis and eye involvement in young children.

The current classification of juvenile rheumatoid arthritis (JRA) consists of several distinct subsets. We describe 6 children (2 boys, 4 girls, mean age 3.7 years, range 2.0-4.9 years) with arthritis and eye involvement associated with infection with Chlamydia trachomatis. In some of the children, the clinical picture was similar to early onset pauciarticular JRA: onset within the first 4 years of life, predominance of girls, pauciarticular arthritis, subacute uveitis, and presence of antinuclear antibodies. Joint involvement was pauciarticular in 4 patients and polyarticular in 2. Two patients had clinical symptoms of Reiter's disease. Further investigations of this post chlamydial associated syndrome should be performed to establish appropriate diagnostic, therapeutic and prognostic measures.     

The co-occurrence of Reiter's syndrome and acquired immunodeficiency

Thirteen patients who had the co-occurrence of severe Reiter's syndrome and the acquired immunodeficiency syndrome (AIDS) or its syndromes were studied. The arthritis was reactive in three patients and without defined cause in the others. Nine patients had HLA-B27. The two syndromes appeared simultaneously in four patients, suggesting a common biologic process, and in the others the immunodeficiency either preceded or followed the arthritis. Reiter's syndrome occurring in the setting of this profound immunodeficiency suggests that helper T cells were not involved in the pathogenesis of the rheumatic disease. Difficulties were encountered in the diagnosis of either syndrome in the presence of the other. Two patients with Reiter's syndrome developed Kaposi's sarcoma and fulminant AIDS after receiving methotrexate, which emphasizes the need for caution in the use of immunosuppressive therapy in Reiter's syndrome. An additional patient with undifferentiated spondylarthropathy subsequently developed psoriasis in conjunction with the onset of AIDS.     

Evaluation of revised International League of Associations for Rheumatology classification criteria for juvenile idiopathic arthritis in Spanish children (Edmonton 2001)

OBJECTIVE: To evaluate the revised (Edmonton 2001) International League of Associations for Rheumatology (ILAR) classification criteria for Juvenile Idiopathic Arthritis (JIA) in a cohort of Spanish children. METHODS: One hundred twenty-five patients with chronic arthritis categorized according to traditional criteria and to the first revision of ILAR JIA criteria (Durban 1997) were reclassified according to the second JIA criteria revision (Edmonton 2001). RESULTS: Edmonton criteria allocated 92% of the patients classified by traditional criteria in their corresponding ILAR categories. Most patients with systemic (94%), pauciarticular (91%) and polyarticular (88%) juvenile chronic arthritis as well as those with juvenile spondyloarthropathy (94%) were reclassified in the corresponding ILAR categories. Two children with probable psoriatic arthritis (PsA) were reclassified in the rheumatoid factor-negative (RF-) polyarthritis category, whereas only one of 2 children with definite PsA could be allocated to the ILAR PsA class. Ten patients (8%) constituted the undifferentiated arthritis group, 8 because of psoriasis in a first-degree relative, one because of the presence of RF in a girl with oligoarthritis, and another because of psoriasis in a boy who was HLA-B27-positive. In comparison with the Durban JIA criteria the Edmonton revision decreased the number of patients whose arthritis fulfilled criteria in no category or in 2 or more categories (from 19 to 10), and delineated better the population included in the RF- polyarthritis category. CONCLUSION: The Edmonton criteria made the ILAR classification more transparent and easy to apply. Family history of psoriasis was responsible for most allocations to the undifferentiated arthritis category (8/10).     

HLA-B27 expression and reactive arthritis susceptibility in two patient cohorts infected with Salmonella Typhimurium

Background: Reactive arthritis (ReA) is an inflammatory arthritis triggered by certain gastrointestinal and genitourinary infections. Single source outbreaks of triggering infections provide an opportunity to elucidate host susceptibility factors in this disease. Aim: To determine the role of Major Histocompatibility Complex (MHC) Class I alleles in ReA susceptibility after two large single source outbreaks of Salmonella Typhimurium gastroenteritis. Methods: A questionnaire screening for features of ReA and a request for HLA class I typing were sent to all patients affected by two single source outbreaks of S. Typhimurium gastroenteritis. Individuals with arthritis of recent onset were interviewed, examined and diagnostic criteria for ReA applied. Results: Nineteen cases of reactive arthritis, 11 female, were diagnosed in the 424 respondents with S. Typhimurium gastroenteritis from both outbreaks. Clinical features of the arthritis were similar to those described after other large single source outbreaks of Salmonella infection. HLA‐B27 was expressed by only two of the 19 ReA patients and therefore did not predict susceptibility to this form of arthritis. Caucasians were, however, more likely to develop reactive arthritis than Asians. Conclusions: In this study, susceptibility to ReA was not increased in HLA‐B27 positive individuals or males but was greater in those of Caucasian descent.